Glycosaminoglycan Mimetic Scaffolds

Abstract

Sodium cellulose sulfate (NaCS) is employed as a novel GAG mimetic. Schwann cells (SCs) could be used in combination with a scaffold because the SCs can secrete neurotrophic factors stimulating neuron survival and extension of axons. Furthermore, the conduit may be used alone or combination with Schwann cells for spinal cord repair. In addition, the conduit also can be used for peripheral nerve repair. Also described herein are compositions and methods useful for promoting the growth and/or differentiation and/or repair of a cell and/or tissue in the peripheral nervous system, central nervous system, and specifically the spinal cord. In certain aspects, the present disclosure includes a scaffold supporting and promoting growth, differentiation, and/or regeneration and repair. The scaffold in one embodiment closely mimics the natural extracellular matrix (ECM) of the spinal cord.

What is claimed is: 
     
         1 . A composition for a glycosaminoglycans (GAGs) mimetic scaffold, comprising:
 a sodium cellulose sulfate (NaCS) scaffold containing aligned fibers; and wherein, the scaffold promotes spinal cord repair or peripheral nerve repair.   
     
     
         2 . The composition of  claim 1 , further includes:
 at least one Schwann Cell (SC) disposed about or in the scaffold; and wherein, the SCs stimulate axon growth.   
     
     
         3 . The composition of  claim 1 , wherein the NaCS is either partial or fully sulfated and the scaffold mimics an in vivo spinal cord extracellular matrix (ECM). 
     
     
         4 . The composition of  claim 1 , wherein the NaCS has a varying degree and a pattern of sulfation similar to a native GAGs for forming a GAGs mimetic scaffold. 
     
     
         5 . The composition of  claim 4 , wherein the native GAGs is selected from a group consisting of chondroitin-6-sulfate or chondroitin sulfate-C (CS-C), chondroitin-2,6-sulfate or chondroitin sulfate-D (CS-D), and any combination thereof. 
     
     
         6 . The composition of  claim 4 , wherein the GAGs mimetic scaffold is selected from a group consisting of a partial sulfated sodium cellulose sulfate (pNaCS), a fully sulfated sodium cellulose sulfate (fNaCS), and any combination thereof. 
     
     
         7 . The composition of  claim 6 , wherein the partial sulfated sodium cellulose sulfate (pNaCS) contains a sulfate group on a  6 th position of a glucose unit. 
     
     
         8 . The composition of  claim 6 , wherein the fully sulfated sodium cellulose sulfate (fNaCS) contains a sulfate group on a 2nd, 3rd, and 6th positions of a glucose unit. 
     
     
         9 . The composition of  claim 8 , further including at least one Schwann Cell (SC) disposed about or in the GAG mimetic scaffold for promoting and directing axonal growth. 
     
     
         10 . The composition of  claim 9 , wherein the scaffold is fabricated using an electrospinning technique. 
     
     
         11 . The composition of  claim 1 , wherein neurite growth on the scaffold depends on the degree and pattern of sulfation. 
     
     
         12 . The composition of  claim 1 , wherein the average scaffold thickness is about  0 . 2 mm 
     
     
         13 . The composition of  claim 1 , wherein the scaffold is either a partial sulfated sodium cellulose sulfate (pNaCS) with 0.5 sulfates per glucose unit or a fully sulfated sodium cellulose sulfate (fNaCS) with 3 sulfates per glucose unit. 
     
     
         14 . The composition of  claim 13 , wherein the scaffold further includes either gelatin or gelatin/polycaprolactone (Gel/PCL) at the ratio of 80:20 with a 0.25% concentration of fNaCS or pNaCS. 
     
     
         15 . The composition of  claim 1 , wherein the scaffold further includes a crosslinked conduit to improve hydrolytic stability in a physiological condition. 
     
     
         16 . A method for preparing a glycosaminoglycans (GAGs) mimetic scaffold, comprising:
 dissolving a sodium cellulose sulfate (NaCS) conduit with a varying degree of sulfation in 15% deionized (DI) water to form a dissolved solution;   mixing the dissolved solution with a solution of either 100% bovine gelatin or a 80:20 ratio of gelatin: a poly-caprolactone (PCL) in an acetic acid (AA) and a 2,2,2-trifluoroethanol (TFE) to form a resultant solution;   electrospinning the resultant solution for preparing a scaffold containing aligned fibers; and   wherein, the scaffold promotes spinal cord repair or peripheral nerve repair.   
     
     
         17 . The method of  claim 16 , further includes:
 disposing at least one Schwann Cell (SC) about or in the scaffold; and   wherein, the SC stimulates extension of axons.   
     
     
         18 . The method of  claim 16 , wherein the varying degree of sulfation includes a partial sulfated sodium cellulose sulfate (pNaCS) with 0.5 sulfates per glucose unit or a fully sulfated sodium cellulose sulfate (fNaCS) with 3 sulfates per glucose unit. 
     
     
         19 . The method of  claim 16 , wherein the mixing of the 80:20 ratio of gelatin further includes:
 preparing in the trifluoroethanol (TFE), the acetic acid (AA), and the deionized water at a ratio of 60:25:15 either a 25% w/v gelatin or a 22% w/v gelatin/polycaprolactone (Gel/PCL) at the ratio of 80:20 with a 0.25% of a fully sulfated sodium cellulose sulfate (fNaCS) or a partial sulfated sodium cellulose sulfate (pNaCS).   
     
     
         20 . A method for preparing a glycosaminoglycans (GAGs) mimetic scaffold, comprising:
 preparing a sodium cellulose sulfate (NaCS) scaffold containing aligned fibers;   disposing at least one Schwann Cell (SC) about or in the scaffold; the SC promotes axon growth;   wherein, the scaffold promotes spinal cord repair or peripheral nerve repair; and   wherein, the NaCS is either a partially sulfated sodium cellulose sulfate (pNaCS) with 0.5 sulfates per glucose unit or a fully sulfated sodium cellulose sulfate (fNaCS) with 3 sulfates per glucose unit at a concentration of fNaCS or pNaCS of 0.25%.